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Published on: January 12, 2020
NOTCH1, NOTCH3, NOTCH4, and JAG2 protein levels in human endometrial cancer
Aušra Sasnauskienė1, Violeta Jonušienė1, Aurelija Krikštaponienė2
1Department of Biochemistry and Molecular Biology, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania.
Background And Objective:
Notch signaling is a conserved developmental pathway, which plays an important role in the regulation of cell proliferation, differentiation and death. Deregulation of Notch pathway has been connected with the carcinogenesis in a variety of cancers. The aim of this study was to investigate the level of the Notch signaling pathway proteins (NOTCH1, 3, 4 and JAG2) in the samples from human endometrial cancer.
Materials And Methods:
The amount of the Notch receptors NOTCH1, 3, 4 and ligand JAG2 protein was determined by Western blot analysis in the samples from stage I endometrial cancer and adjacent nontumor endometrial tissue of 22 patients.
Results:
The level of NOTCH4 receptor was 1.7 times lower in stage I endometrial cancer as compared with the healthy tissue of the same patients (P=0.04). The protein level of ligand JAG2 was significantly reduced by 2.5 times in stage IB endometrial adenocarcinoma samples (P=0.01). It was reduced in the majority of stage IB adenocarcinomas. There were no significant changes in the protein amount of NOTCH1 and NOTCH3 receptors comparing stage I endometrial adenocarcinoma and healthy tissues.
Conclusions:
The reduced amount of NOTCH4 and JAG2 proteins and the decreased level of mRNA coding Notch proteins, as reported in our previous studies, supports the notion that Notch pathway has rather tumor-suppressive than oncogenic role in human endometrial cancer cells. It suggests that Notch pathway activation is a potential therapeutic target.
Insights
In endometrial cancer, Notch signaling proteins NOTCH4 and JAG2 were found at lower levels, suggesting a tumor-suppressive role for this pathway and indicating potential therapeutic targets.
Area of Science:
- Cellular signaling pathways
- Cancer biology
- Molecular oncology
Background:
- Notch signaling is crucial for cell development and is implicated in various cancers.
- Deregulation of the Notch pathway is linked to carcinogenesis.
Purpose of the Study:
- To investigate the protein levels of Notch signaling pathway components (NOTCH1, 3, 4, and JAG2) in human endometrial cancer.
- To determine the role of Notch signaling in endometrial carcinogenesis.
Main Methods:
- Western blot analysis was used to quantify protein levels.
- Samples included stage I endometrial cancer and adjacent non-tumor tissues from 22 patients.
Main Results:
- NOTCH4 receptor levels were 1.7 times lower in endometrial cancer tissues (P=0.04).
- JAG2 ligand levels were significantly reduced by 2.5 times in stage IB adenocarcinoma (P=0.01).
- No significant changes were observed for NOTCH1 and NOTCH3 receptors.
Conclusions:
- Reduced NOTCH4 and JAG2 protein levels suggest a tumor-suppressive role for the Notch pathway in endometrial cancer.
- These findings highlight Notch pathway activation as a potential therapeutic strategy for endometrial cancer.
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